Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and often fatal form of interstitial lung disease. IPF is the most common form of idiopathic interstitial pneumonias. IPF causes the loss of lung epithelial cells, replacement of normal functional tissue, accumulation of fibroblasts and myofibroblasts, extracellular matrix deposition, alteration of lung architecture, pulmonary hypertension leading to substantial impairment of respiration and gas exchange often resulting in patient morbidity and mortality.
Treatment of IPF represents a major clinical challenge since this disorder does not have reliable therapeutic options and an effective therapy has yet to be identified and developed. Patient may ultimately require supportive oxygen therapy or pulmonary transplantation. Consequently, the development of a novel effective treatment of this devastating disease represents a very important and urgent task.
Prostaglandin E2 (PGE2), a cyclooxygenase-derived lipid mediator, has attracted considerable attention for its role in the development and progression of IPF and as a possible therapeutic for this disease. A role for PGE2 in the treatment of IPF is based on the very specific and unique role that PGE2 plays in the lungs making “the lung as a privileged site for the beneficial actions of PGE2.” In other organs and tissues, PGE2 often acts as a potent pro-inflammatory mediator and is involved in pathogenesis of many inflammatory diseases. In contrast, in the lungs, PGE2 limits the immune-inflammatory response, inhibits specific lung fibroblast functions, their proliferation and synthesis of matrix proteins such as collagen. Consequently, PGE2 potentially can be used for the treatment of IPF. Moreover, it was recently shown that a synthetic analog of PGE2 (16,16-dimethyl-PGE2) recently was tested using in a model of pulmonary fibrosis (intratracheal administration of bleomycin) with promising results for treatment of IPF.
Systemic delivery of PGE2 has several limitations including the short half-life in the blood stream, low accumulation in the lungs and possible adverse side effects on other organs and tissues. In contrast, local inhalation delivery of PGE2 directly to the lungs has the potential to enhance the treatment of IPF (or other pulmonary conditions, such as, pulmonary fibrosis, interstitial lung disease, idiopathic interstitial pneumonia, and asthma) by increasing its local pulmonary concentration and preventing (or at least limiting) its penetration into the bloodstream and distribution to other healthy organs. However, free native PGE2 cannot be delivered into the lungs by inhalation requiring a special dosage form or delivery system that can be inhaled. Accordingly, there is a need to allow delivery of PGE2 into the lungs.